Premium
Effect of a Single Gemfibrozil Dose on the Pharmacokinetics of Rosuvastatin in Bile and Plasma in Healthy Volunteers
Author(s) -
Bergman Ebba,
Matsson Elin M.,
Hedeland Mikael,
Bondesson Ulf,
Knutson Lars,
Lennernäs Hans
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009357432
Subject(s) - gemfibrozil , pharmacokinetics , rosuvastatin , bioavailability , pharmacology , bioequivalence , plasma concentration , chemistry , medicine , cholesterol
The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum‐proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC plasma, 200min ) by 1.56‐fold (95% confidence interval, 1.14–2.15). The interaction was less pronounced in this single‐dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 μM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.